Functional Crosstalk between Type I and II Interferon through the Regulated Expression of STAT1

Abstract

Author SummaryCells of the immune system release interferons (IFNs) in response to pathogens or tumor cells; these proteins signal to other immune cells to initiate the body's defense mechanisms. The two classes of IFNs—types I and II—have different receptors and distinct effects on the cells; however, there is “crosstalk” between them. In particular, small quantities of type I IFN can “prime” cells to produce a robust response to type II IFN. In this paper, we provide evidence to explain the molecular basis of this crosstalk. We show that continuous expression of the transcriptional activator c-Jun is responsible for producing basal, priming levels of a type I IFN; this signals to immune cells with the type I IFN receptor (IFNAR1) to maintain expression of STAT1 inside these cells. STAT1 is a key factor for immune cell responses to type II IFN. Thus, signaling by low levels of type I IFN primes the cells with sufficient STAT1 to respond robustly to a subsequent type II IFN signal. This work provides an alternative explanation of the priming phenomenon to a previous proposal that the ligand-bound type I receptor, IFNAR1, acts as a component of the type II IFN receptor.